Medical device with sponge coating for controlled drug release

ABSTRACT

The medical devices of the invention comprise an expandable portion which is covered with a sponge coating for release of at least one biologically active material. The sponge coating is made of a non-hydrogel polymer having a plurality of voids. The device can further include means for infusing or expelling the biologically active material or drug into the voids. The drug is delivered to the body lumen of a patient by expelling the drug and inflating or expanding the expandable portion of the catheter or device.

CROSS REFERENCE TO RELATED APPLICATION

This application is a Continuation of application Ser. No. 10/071,400filed Feb. 7, 2002, which is a divisional of application Ser. No.09/060,071, filed Apr. 14, 1998 (now U.S. Pat. No. 6,364,856), both ofwhich are incorporated herein by reference in their entirety.

FIELD OF THE INVENTION

This invention relates generally to medical devices for delivering abiologically active material to a desired location within the body of apatient. More particularly, the invention is directed to medical deviceshaving a sponge coating comprising a non-hydrogel polymer and aplurality of voids therein, optionally formed by eluting a particulatematerial from the polymer. The sponge coating is capable of being loadedwith a drug, e.g., infusing or placing the drug into the voids, forrelease into the body upon expansion of the coated portion of themedical device.

BACKGROUND OF THE INVENTION

For certain diseases which are localized to a particular part of thebody, the systemic administration of drugs for the treatment of thesediseases may not be preferred because of the inefficiencies associatedwith the indirect delivery of the drugs to the afflicted area. Instead,it may be preferred that the drug be directly applied to the diseasedtissue. However, such localized delivery of drugs to the walls oflumens, such as blood vessels and ducts, can be problematic since lumensare involved in the transport of body fluids, which tend to carry thedrug away from the afflicted area. Thus, there is a need for devices andmethods for the localized delivery of drugs to afflicted tissue,especially body lumens.

A number of methods for delivering drugs to body lumens or vesselsinvolve the use of catheters having expandable portions, such as aballoon, disposed on the catheter. For instance, U.S. Pat. No. 5,304,121to Sahatjian, PCT application WO 95/03083 to Sahatjian et al. and U.S.Pat. No. 5,120,322 to Davis et al. describe medical devices in which theexterior surface of the device is coated with a swellable hydrogelpolymer. A solution of a drug to be delivered to the afflicted tissue isincorporated into the hydrogel. The drug is held within the matrix ofthe hydrogel. In the case where the medical device is a ballooncatheter, the drug is delivered by inserting the catheter into the bodylumen and expanding the coated balloon against the afflicted tissue ofthe lumen to force the drug from the hydrogel into the tissue.

However, these hydrogel coated devices have certain disadvantages. Inparticular, since the hydrogels are water-based, only hydrophilic drugscan be effectively incorporated into the hydrogels. Therefore, a numberof useful hydrophobic biologically active materials or drugs, such asdexamethasone, cannot be suitably embedded into these hydrogels. Hence,there is a need for a coating for a medical device which can effectivelyincorporate such hydrophobic drugs in relatively large quantities.

Also, the application of the hydrogel coating to the balloon usuallyinvolves multiple steps because most balloon materials are hydrophobicso that a hydrogel usually has poor adhesion to the balloon surface.Another disadvantage with hydrogels is that the hydrogels will tend tobe tacky or sticky when they are not fully hydrated. When a hydrogel isnot in its fully hydrated state, it can stick to the surface of thepackaging material or protection sheath for the coated device and makethe insertion or implantation of the device difficult.

Moreover, even when prostheses having a drug containing coating areimplanted into the body, it is desirable to apply a dose of the drug tothe implantation site in addition to that contained in the coating.Hence, there is a need for a device which can deliver a prosthesis aswell as a dose of the drug to the implantation site.

SUMMARY OF THE INVENTION

These and other objectives are accomplished by the present invention. Toachieve the aforementioned objectives, we have invented a medical deviceand a method for making and using such device for the localized deliveryof biologically active materials as well as implanted prostheses to apatient.

The medical devices of the invention comprise an expandable portionwhich is covered with a sponge coating for release of at least onebiologically active material. The sponge coating is made of anon-hydrogel polymer having a plurality of voids. The void space of thesponge coating is greater than about 60% of the volume of the spongecoating. The device can further include means for infusing thebiologically active material or drug into the voids.

In an embodiment of the invention, the device is a catheter having anexpandable portion which can be inflated or expanded by inflationpressure to fill the cross-section of the body lumen and engage thetissue of the body lumen. Upon expansion, the biologically activematerial, which has been placed into the voids of the sponge coating, isreleased into the body. The catheter can also be capable of performingan angioplasty procedure at pressures of greater than 6 atm anddelivering an implantable prosthesis such as a stent.

In another embodiment, the infusion means of the catheter can furthercomprise an inflation lumen connected to a balloon with pores. Theballoon is filled with a biologically active material. When the balloonis inflated, the biologically active material infuses into the voids ofthe sponge coat and can be released into the body lumen.

In yet another embodiment of the present invention, a catheter has anexpandable portion which comprises a reservoir defined by a porousmembrane. The porous membrane or film is used to separate the spongecoating and the reservoir. The reservoir can be connected to a reservoirlumen, thereby allowing the reservoir to be filled with a biologicallyactive material. Disposed about the porous membrane of the reservoir isa sponge coat comprising a non-hydrogel polymer having a plurality ofvoids formed by eluting a particulate material from the polymer. Elutionof the particulate material means that such material becomes dissolvedor suspended in a surrounding solvent or fluid. The catheter can furtherinclude a balloon disposed within the reservoir, wherein the balloon isconnected to an inflation lumen. When the balloon is expanded thebiologically active material of the reservoir is expelled or “squeezedout” through the porous membrane and infused into the voids of thesponge coat. Upon further expansion the biologically active material isreleased from the sponge coating into the body lumen.

Furthermore, in another embodiment of the invention the medical device,which is coated with a sponge coating is an expandable stent. The stentcan be a self-expanding or balloon expandable stent.

The devices of the present invention are prepared by applying a spongecoating composition to a surface of an expandable portion of a device.The sponge coating composition comprises a non-hydrogel polymerdissolved in a solvent and an elutable particulate material. After thesponge coating composition is cured, it is exposed to a solvent, e.g.,water, which causes the particulate material to elute from the polymerleaving a sponge coating having a plurality of voids therein. The spongecoating is then exposed to a biologically active material to load thesponge coating with such material. Such material may be loaded into thecoating by diffusion or other means.

DESCRIPTION OF THE DRAWINGS

FIGS. 1 a and 1 b depict cross-sectional views of an embodiment of adrug delivery balloon catheter at the afflicted area of the lumen in itsunexpanded and expanded state, respectively.

FIGS. 2 a and 2 b depict cross-sectional views of an embodiment of adrug delivery catheter having a drug reservoir in its unexpanded andexpanded state, respectively.

FIG. 3 depicts a cross-sectional view of an embodiment of a drugdelivery catheter having a balloon containing a drug in its expandedstate.

FIGS. 4 a and 4 b depict a balloon expandable stent prosthesis, in itsunexpanded and expanded state respectively, which is mounted on anexpandable portion of a drug delivery catheter.

FIGS. 5 a and 5 b depict a self-expanding stent prosthesis, in itsunexpanded and expanded state respectively, which is mounted on anexpandable portion of a drug delivery catheter.

FIGS. 6 a-6 c depict a method of preparing the sponge coating for aballoon catheter.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

The medical devices suitable for the present invention include thosehaving at least an expandable portion. Such devices include withoutlimitation balloon catheters and perfusion catheters, which are known tothe skilled artisan.

An embodiment of the present invention is illustrated in FIGS. 1 a and 1b. FIG. 1 a shows a catheter 1 being delivered to the afflicted tissue 9of a body lumen 8. The catheter 1 comprises an expandable portion 2having a balloon 3 disposed about the catheter 1. The outer surface ofthe balloon 3 is covered with a sponge coating 4 of a non-hydrogelpolymer having a plurality of voids 10 therein. A drug 5 is placed intothe voids 10. An inflation lumen 6 is connected to the balloon 3 to fillthe balloon 3 with fluid, such as a liquid, or pressurized gas, and toexpand the balloon 3. A protective sheath 7 can be placed around theexpandable portion 2 to prevent the drug 5 from being inadvertentlyreleased during insertion of the catheter 1 into the body lumen 8.

FIG. 1 b shows the catheter 1 in its deployed state. In FIG. 1 b, theballoon 3 has been expanded to deliver the drug 5. The drug 5 is forcedout of the sponge coating 4 by the expansion of the balloon 3 againstthe body lumen 8. The drug 5 is thereby released into the afflictedtissue 9 for treatment. In the case of an expanded balloon, as shown inFIG. 1 b, the expansion of the balloon causes the sponge coating layerto become thinner, resulting in an expulsion of the drug from thecoating 4.

Another embodiment of the invention is depicted in FIGS. 2 a and 2 b.The catheter 1 of this embodiment comprises an expandable portion 2having a reservoir 12 disposed about a balloon 3 connected to aninflation lumen 6. The reservoir 12 is connected to a reservoir lumen 11which can be used to fill the reservoir 12 with the drug 5. A porousmembrane 13 defines the reservoir's outer surface. A sponge coating4—having voids 10 therein covers the outer surface of the reservoir 12,i.e., outside the porous membrane 13.

The drug 5 is delivered to the afflicted tissue 9 by filling thereservoir 12 through the reservoir lumen 11 with a drug 5. As theballoon 3 is expanded, drug 5 in the reservoir 12 passes or is forcedthrough the porous membrane 13 into the voids 10 of the sponge coating4. Additional expansion of the balloon 3 causes the drug 5, which is inthe sponge coating 4 to he released from the sponge coating 4 into theafflicted tissue 9. A perfusion lumen can be included in the catheter 1to sustain the inflation of the balloon 3, and infusion of the drug 5into the sponge coating 4.

One of the advantages of infusing the sponge coating with the drug isthat such infusion maximizes the amount of drug delivered to theafflicted area of the body lumen and reduces the amount of drug which islost to the lumen fluid, e.g., blood. Also, infusion of the spongecoating with the drug permits the more even distribution of the drugonto the afflicted lumen tissue without damaging such tissue.

Also, a control unit (not shown) can be included to synchronize theinflation of the balloon 3 with the delivery of the drug 5 and thedeflation of the balloon 3 with the infusion of the drug 5 into thesponge coating 4. Such a control unit would manipulate the timing of theinfusion of the drug 5 into the sponge coating 4 when the balloon 3 isbeing deflated instead of when it is being inflated. Synchronizationof-infusion with deflation minimizes undesired “jetting” or excessrelease of large quantities of drug 5 into the body lumen.

FIG. 3 illustrates yet another embodiment of a catheter 1 in itsexpanded state wherein the balloon 3 and reservoir 12 of the embodimentof FIGS. 2 a and 2 b are combined. In this embodiment, drug 5 is placedinto the balloon 3 through the inflation lumen 6 to expand the balloon3. In other words by filling the balloon 3 with a fluid or compositioncontaining the drug 5, the balloon 3 is expanded. The force of expansioncauses the drug 5 in the balloon 3 to infuse the drug 5 into the voids10 of the sponge coating 4. By expanding the balloon 3 further the drug5 can be released from the sponge coating 4 into afflicted tissue 9.

In addition, the catheters of the invention can be used to deliver animplantable prosthesis such as an expandable stent. The expandablestents which can be used in this invention include self-expanding stentsand balloon expandable stents. Examples of self-expanding stents usefulin the present invention are illustrated in U.S. Pat. Nos. 4,655,771 and4,954,126 issued to Wallsten and 5,061,275 issued to Wallsten et al.Examples of appropriate balloon-expandable stents are shown in U.S. Pat.No. 4,733,665 issued to Palmaz, U.S. Pat. No. 4,800,882 issued toGianturco and U.S. Pat. No. 4,886,062 issued to Wiktor.

Since the stent is implanted in the body, it can be covered with adrug-releasing coating which provides long term delivery of the drug.Generally, these coatings comprise a drug incorporated into a polymericmaterial. Such drug-releasing coatings are described in U.S. Pat. No.5,464,650 to Berg et al.

The expandable stent may be formed from polymeric, metallic and/orceramic materials. Suitable polymeric materials include withoutlimitation poly-L-lactic acid, polycarbonate, and polyethyleneterephthalate.

FIGS. 4 a and 4 b show the delivery and deployment of a balloonexpandable stent 15 by a catheter 1 coated with a sponge coating 4having a drug 5 infused into the voids 10 of the sponge coating 4. Thestent 15 is disposed on the expandable portion 2 of the catheter 1 fordelivery as in FIG. 4 a. The stent can also be coated with a spongecoating, particularly one where the particulate material is a drug. Thestent 15 is implanted by expanding the balloon 3 to force open thestent. Also, as shown in FIG. 4 b, when the stent 15 is deployed,expansion of the balloon 3 causes the drug 5 to infuse into the voids 10of the sponge coating 4 and to be released into the body lumen 8.

The delivery and deployment of a self-expanding stent 16 by a coatedcatheter 1 of the present invention is illustrated in FIGS. 5 a and 5 b.In FIG. 5 a, a sheath 7 is placed around the stent 16, which is disposedabout the expandable portion 2 of the catheter 1, to maintain the stent16 in a contracted state for delivery. After the stent 16 is placed toits implantation site, the sheath 7 is withdrawn to deploy theself-expanding stent 16. While or after the stent 16 expands, theballoon 3 is expanded to further dilate the stent and release the drug 5from the sponge coating 4.

The following is a more detailed description of suitable materials andmethods useful in producing the sponge coatings of the invention.

The non-hydrogel polymer(s) useful for forming the sponge coating shouldbe ones that are biostable, biocompatible, particularly during insertionor implantation of the device into the body and avoids irritation tobody tissue. Non-hydrogel polymers are polymers that when a drop ofwater is added on top of a film of such polymer, the drop will notspread. Examples of such polymers include without limitationpolyurethanes, polyisobutylene and its copolymers, silicones, andpolyesters. Other suitable polymers include polyolefins,polyisobutylene, ethylene-alphaolefin copolymers, acrylic polymers andcopolymers, vinyl halide polymers and copolymers such as polyvinylchloride, polyvinyl ethers such as polyvinyl methyl ether,polyvinylidene halides such as polyvinylidene fluoride andpolyvinylidene chloride, polyacrylonitrile, polyvinyl ketones, polyvinylaromatics such as polystyrene, polyvinyl esters such as polyvinylacetate, copolymers of vinyl-monomers, copolymers of vinyl monomers andolefins such as ethylene-methyl methacrylate copolymers,acrylonitrile-styrene copolymers, ABS resins, ethylene-vinyl acetatecopolymers, polyamides such as Nylon 66 and polycaprolactone, alkydresins, polycarbonales, polyoxyethylencs, polyimides, polyethers, epoxyresins, polyurethanes, rayon-triacetate, cellulose, cellulose acetate,cellulose butyrate, cellulose acetate butyrate, cellophane, cellulosenitrate, cellulose propionate, cellulose ethers, carboxymethylcellulose, collagens, chitins, polylaetic acid, polyglycolic acid, andpolylactic acid-polyethylene oxide copolymers.

Since the polymer is being applied to a part of the medical device whichundergoes mechanical challenges, e.g., expansion and contraction, thepolymers are preferably selected from elastomeric polymers such assilicones (e.g. polysiloxanes and substituted polysiloxanes),polyurethanes, thermoplastic elastomers, ethylene vinyl acetatecopolymers, polyolefin elastomers, polyisobutylene and its copolymersand EPDM rubbers. The polymer is selected to allow the coating to betteradhere to the surface of the expandable portion of the medical devicewhen it is subjected to forces or stress.

Furthermore, although the sponge coating can be formed by using a singletype of polymer, various combinations of polymers can be employed. Theappropriate mixture of polymers can be coordinated with biologicallyactive materials of interest to produce desired effects when coated on amedical device in accordance with the invention.

The elutable particulate materials which can be incorporated into thepolymer include without limitation polyethylene oxide, polyethyleneglycol, polyethylene oxide/polypropylene oxide copolymers,polyhydroxyethyl methacrylate, polyvinylpyrrolidone, polyacrylamide andits copolymers, salts, e.g., sodium chloride, sugars, and elutablebiologically active materials such as heparin.

The amount of elutable particulate material that is incorporated intothe polymer should range from about 20% to 90% by weight of the spongecoating and preferably, from about 50% to 90%. The average particle sizeof the elutable material can range from 1-100 microns and preferablyfrom about 2 to 15 microns.

The solvent that is used to form the mixture or slurry of polymer andelutable particulate materials includes ones which can dissolve thepolymer into solution and do not alter or adversely impact thetherapeutic properties of the biologically active material employed.Examples of useful solvents for silicone include tetrahydrofuran (THF),chloroform and dichloromethane.

The composition of polymer and elutable particulate material can beapplied to the expandable portion of the medical device in a variety ofways. For example, the composition can be spraycoated onto the device orthe device can be dipped into the composition. One of skill in the artwould be aware of methods for applying the coating to the device. Thethickness of the sponge coating can range from about 25 μm to 0.5 mm.Preferably, the thickness is about 30 m to 100 μm.

After the composition is applied to the device, it should be cured toproduce a polymer containing the particulate material and to evaporatethe solvent. Certain polymers, such as silicone, can be cured atrelatively low temperatures (e.g. room temperature) in what is known asa room temperature vulcanization (RTV) process. More typically, thecuring/evaporation process involves higher temperatures so that thecoated device is heated in a oven. Typically, the heating occurs atapproximately 90° C. or higher for approximately 1 to 16 hours whensilicone is used. For certain coatings the heating may occur attemperatures as high as 150° C. The time and temperature of heating willof course vary with the particular polymer, drugs, and solvents used.One of skill in the art is aware of the necessary adjustments to theseparameters.

To elute the particulate material from the polymer, a solvent is used.The device can be soaked in the solvent to elute the particulatematerials. Other methods of eluting the particulate are apparent tothose skilled in the art.

The choice of the solvent depends upon the solubility of the elutableparticulate material in that solvent. For instance, for water-solubleparticulate materials such as heparin, water can be used. For elutableparticulate materials that can be dissolved in organic solvents, suchorganic solvents can be used. Examples of suitable solvents, withoutlimitation, include ethanol, dimethyl sulfoxide, etc.

After the particulate material is eluted from the polymer, the medicaldevice can be optionally sterilized. Depending upon the nature of thedrug used, sterilization of the device can occur before or after thedrug is loaded into the sponge coating. Methods of sterilization areknown in the art. For example, the devices can be sterilized by exposureto gamma radiation at 2.5-3.5 Mrad or by exposure to ethylene oxide.

As shown in FIGS. 6 a-6 c, in one method for making the sponge coating100, a mixture or slurry comprising a non-hydrogel polymer 101, anelutable particulate material 102 and a solvent is applied to anexpandable portion of the medical device. The device is then exposed toan aqueous or organic solvent to elute the particulate material 102 fromthe polymer 101 to form a plurality of voids 103 in the polymer 101. Abiologically active material or drug 104 is then loaded or placed intothe voids 103 prior to delivery of the drug 104 to the body.

To load the sponge coating with the biologically active material ordrug, a composition comprising the drug is applied to the spongecoating. The drug can be loaded just prior to use of the medical device.The drug can be loaded by immersing the sponge coated portion of thedevice into the drug solution and allowing the drug to diffuse into thevoids of the sponge coating.

In order to place or infuse the drug into the sponge coating, the drugshould be dissolved or dispersed into a solvent. The sponge coatedportion of the device is then immersed into the drug solution. Due todiffusion, the drug will enter the voids of the sponge coating. Afterthe solvent is permitted to evaporate, a drug coated device is formed.The device can then be sterilized. If the drug can not be sterilized,the physician can load the drug just before the insertion orimplantation procedure is performed.

Alternatively, the medical device can be constructed such that the drugcan be infused from within the medical device as described in theabove-mentioned embodiments. For instance, the catheter can include adrug reservoir whereby inflation of the balloon causes the drug in thereservoir to infuse into the sponge coating.

Furthermore, in another method for making the sponge coating, thecoating can be formed in viva, i.e., while the device, which is coatedwith a polymer and an elutable particulate material, is, inserted orimplanted in the body. To prepare such a coating, particulates, e.g.,hydrophilic or lipophobic drug particles are mixed with non-hydrogelpolymeric materials. The surface of the expandable portion of themedical device, such as a balloon, is then coated with this mixture.After the coated device is implanted or inserted into the body, bodyfluid which contacts the coating permeates into the coating, therebyswelling the coating and dissolving the drug. Some of the drug is theneluted into the body fluid. When the balloon is inflated, additionaldrug is forced out from the coating and directed to the afflicted bodylumen. In such a manner, a significant quantity of drug can be deliveredto the body lumen.

Suitable biologically active materials that can be used in thisinvention include without limitation glucocorticoids (e.g.dexamethasone, betamethasone), heparin, hirudin, angiopeptin, aspirin,growth factors, antisense agents, anti-cancer agents, anti-proliferativeagents, oligonucicotides, and, more generally, antiplalelet agents,anti-coagulant agents, antimitotic agents, antioxidants, anti-metaboliteagents, and anti-inflammatory agents could be used. Antiplatelet agentscan include drugs such as aspirin and dipyridamole. Aspirin isclassified as an analgesic, antipyretic, anti-inflammatory andantiplatelet drug. Dipyridamole is a drug similar to aspirin in that ithas anti-platelet characteristics. Dipyridamole is also classified as acoronary vasodilator. Anticoagulant agents can include drugs such asheparin, protamine, hirudin and tick anticoagulant protein. Anti-canceragents can induce drugs such as taxol, and its analogs or derivatives,antioxidant agents can include probucol. Anti-proliferative agents caninclude drugs such as amlodipine and doxazosin. Anlimitotic agents andanlimelabolite agents can include drugs such as methotrexate,azathioprine, vincristine, vinblastine, 5-fluorouracil, adriamycin andmutamycin. Antibiotic agents can include penicillin, cefoxitin,oxacillin, tobramycin, and gentamicin. Suitable antioxidants includeprobucol. Also, genes or nucleic acids, or portions thereof can be used.Such genes or nucleic acids can first be packaged in liposomes ornanoparticles. Furthermore, collagen-synthesis inhibitors, such astranilast, can be used.

The description contained herein is for purposes of illustration and notfor purposes of limitation. Changes and modifications may be made to theembodiments of the description and still be within the scope of theinvention. Furthermore, obvious changes, modifications or variationswill occur to those skilled in the art. Also, all references cited aboveare incorporated herein, in their entirety, for all purposes related tothis disclosure.

1-46. (canceled)
 47. A medical device having at least an expandableportion which is insertable or implantable into a body lumen of apatient, wherein at least a part of the expandable portion is coveredwith a coating to form an exposed outermost surface for release of atleast one biologically active material; wherein the coating comprises anon-hydrogel polymer having a plurality of voids; wherein the voidscontain at least one biologically active material; and wherein the voidsare formed by eluting a particulate material from the polymer.
 48. Thedevice of claim 47 wherein the device is a catheter for delivering thebiologically active material and wherein the expandable portion isexpandable in response to expansion pressure to substantially fill thecross-section of the lumen and engage the tissue of the lumen.
 49. Thedevice of claim 48 wherein the expandable portion is a balloon.
 50. Thedevice of claim 47 wherein the biologically active material comprises ananti-proliferative agent.
 51. The device of claim 47 wherein thebiologically active material comprises an agent selected from the groupof taxol and its analogs and derivatives.
 52. The device of claim 47wherein the non-hydrogel polymer comprises an elastomeric polymer. 53.The device of claim 47 wherein the non-hydrogel polymer is selected fromthe group of polyisobutylene and its copolymers.
 54. A stent implantableinto a body lumen of a patient, wherein at least a part of the stent iscovered with a coating to form an exposed outermost surface for releaseof at least one biologically active material; wherein the coatingcomprises a non-hydrogel polymer having a plurality of voids; whereinthe voids contain at least one biologically active material; and whereinthe voids are formed by eluting a particulate material from the polymer.55. The stent of claim 54 wherein the stent is a balloon-expandablestent.
 56. The stent of claim 54 wherein the stent is a self-expandingstent.
 57. The stent of claim 54 wherein the biologically activematerial comprises an anti-proliferative agent.
 58. The stent of claim54 wherein the biologically active material comprises an agent selectedfrom the group of taxol and its analogs and derivatives.
 59. The stentof claim 54 wherein the non-hydrogel polymer comprises an elastomericpolymer.
 60. The stent of claim 54 wherein the non-hydrogel polymer isselected from the group of polyisobutylene and its copolymers.
 61. Amethod of delivering a biologically active material to a desiredlocation of a body lumen of a patient comprising: a) forming a coatingon a surface of an expandable portion of a medical device for insertionor implantation into the body of a patient, wherein the expandableportion has a surface which is adapted for exposure to body tissue ofthe patient, the forming done by: i) applying a composition comprising anon-hydrogel polymer and a particulate material to the surface, and ii)exposing the composition to a solvent to elute the particulate materialfrom the polymer to form a plurality of voids therein; b) loading thecoating with the biologically active material; c) delivering theexpandable portion of the medical device to a target location in thebody of the patient; and d) expanding the expandable portion of themedical device at the target location to deliver the biologically activematerial.
 62. The method of claim 61 wherein the expandable portion ofthe medical device comprises a balloon.
 63. The method of claim 61wherein the expandable portion of the medical device comprises a stent.64. The method of claim 61 wherein the biologically active materialcomprises an anti-proliferative agent.
 65. The method of claim 61wherein the biologically active material comprises an agent selectedfrom the group of taxol and its analogs and derivatives.
 66. The methodof claim 61 wherein the non-hydrogel polymer comprises an elastomericpolymer.